Pathophysiology of dyspepsia: an integrative view

Functional dyspepsia (FD) is a chronic, multifactorial gastrointestinal disorder characterized by persistent symptoms in the absence of identifiable structural abnormalities. Its pathophysiology is complex and heterogeneous, involving disturbances in gastric motility, visceral hypersensitivity, gut-brain axis dysfunction, alterations in the microbiota, impairment of the intestinal epithelial barrier, and low-grade inflammation. These mechanisms are frequently associated with impaired gastric accommodation and reduced vagal activity. Such alterations contribute to symptoms including early satiety, nausea, postprandial fullness, and epigastric pain. Low-grade inflammation in the duodenal mucosa, with infiltration of eosinophils and mast cells, has also been documented, contributing to epithelial barrier dysfunction. Post-infectious FD is a recognized subtype associated with prior acute gastrointestinal infections, in which persistent activation of duodenal macrophages and eosinophils is observed. The gut-brain axis plays a critical role in modulating visceral perception, with psychosocial factors, such as anxiety and depression, significantly influencing symptom severity. Abnormal activity in specific brain regions, such as the insula, prefrontal cortex, and anterior cingulate cortex, suggests altered processing of visceral pain. In conclusion, functional dyspepsia should be conceptualized as a disorder resulting from the dynamic interplay between peripheral and central mechanisms, in which immunological, neuromuscular, psychological, and microbial factors converge within a complex pathogenic network. This multidimensional etiology underscores the necessity for a personalized, multimodal approach to diagnosis and management.